A Pharmacokinetic and Safety Study of Paliperidone Palmitate (JNS010) in Participants With Schizophrenia

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Janssen Pharmaceutical K.K.
ClinicalTrials.gov Identifier:
NCT01606254
First received: May 15, 2012
Last updated: May 28, 2013
Last verified: May 2013
  Purpose

The purpose of this study is to assess the pharmacokinetics (the study of the way a drug enters and leaves the blood and tissues over time) and safety of paliperidone palmitate in participants with schizophrenia (psychiatric disorder with symptoms of emotional instability, detachment from reality, often with delusions and hallucinations, and withdrawal into the self).


Condition Intervention Phase
Schizophrenia
Drug: Paliperidone palmitate
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Repeated Dose Study of JNS010 (Paliperidone Palmitate) in Patients With Schizophrenia

Resource links provided by NLM:


Further study details as provided by Janssen Pharmaceutical K.K.:

Primary Outcome Measures:
  • Paliperidone Pre-dose Plasma Concentration (Cpredose) at Day 8 [ Time Frame: Day 8 ] [ Designated as safety issue: No ]
    The pre-dose plasma concentration (Cpredose) at Day 8 is defined as the plasma concentration obtained before a dose is given on Day 8. The mean Cpredose at Day 8 was measured in nanogram per milliliter (ng/ml).

  • Paliperidone Pre-dose Plasma Concentration (Cpredose) at Day 36 [ Time Frame: Day 36 ] [ Designated as safety issue: No ]
    The Cpredose at Day 36 is defined as the plasma concentration obtained before a dose is given on Day 36. The mean Cpredose at Day 36 was measured in ng/ml.

  • Paliperidone Pre-dose Plasma Concentration (Cpredose) at Day 64 [ Time Frame: Day 64 ] [ Designated as safety issue: No ]
    The Cpredose at Day 64 is defined as the plasma paliperidone concentration obtained before a dose is given on Day 64. The mean Cpredose at Day 64 was measured in ng/ml.

  • Paliperidone Pre-dose Plasma Concentration (Cpredose) at Day 92 [ Time Frame: Day 92 ] [ Designated as safety issue: No ]
    The Cpredose at Day 92 is defined as the plasma paliperidone concentration obtained after the treatment interval of the study drug (that is 4 weeks) passed after the final dose (Day 92). The mean Cpredose at Day 92 was measured in ng/ml.

  • Maximum Observed Plasma Concentration (Cmax) of Paliperidone [ Time Frame: Days 1, 8, 15, 22, 36, 50, 64, 67, 71, 74, 78, 85, 92, 106, 120, 134, 162, 190, 218 and early withdrawal ] [ Designated as safety issue: No ]
    The Cmax is defined as maximum observed analyte concentration.

  • Time to Reach Maximum Observed Plasma Concentration (Tmax) of Paliperidone [ Time Frame: Days 1, 8, 15, 22, 36, 50, 64, 67, 71, 74, 78, 85, 92, 106, 120, 134, 162, 190, 218 and early withdrawal ] [ Designated as safety issue: No ]
    The Tmax is defined as actual sampling time to reach maximum observed analyte concentration.

  • Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) [ Time Frame: Days 1, 8, 15, 22, 36, 50, 64, 67, 71, 74, 78, 85, 92, 106, 120, 134, 162, 190, 218 and early withdrawal ] [ Designated as safety issue: No ]
    The AUCtau is a measure of the plasma paliperidone concentration from time zero to end of dosing interval. It is used to characterize drug absorption.

  • Plasma Paliperidone Concentration at Steady State (Css av) [ Time Frame: Days 1, 8, 15, 22, 36, 50, 64, 67, 71, 74, 78, 85, 92, 106, 120, 134, 162, 190, 218 and early withdrawal ] [ Designated as safety issue: No ]
    The Css av is defined as value of average analyte concentration at steady-state (after 4 Intramuscular Injections of Paliperidone Palmitate).

  • Paliperidone Plasma Decay Half-Life (t1/2) [ Time Frame: Days 1, 8, 15, 22, 36, 50, 64, 67, 71, 74, 78, 85, 92, 106, 120, 134, 162, 190, 218 and early withdrawal ] [ Designated as safety issue: No ]
    Plasma decay half-life is the time measured for the plasma concentration to decrease by one half.

  • Number of Participants With Drug-Induced Extrapyramidal Symptoms Scale (DIEPSS) Score at Day 8 [ Time Frame: Day 8 ] [ Designated as safety issue: Yes ]
    The DIEPSS is a scale used to evaluate the severity of drug induced extra-pyramidal symptoms occurring during antipsychotic drug treatment. Scale consists of 8 individual symptom scales with scores ranging from 0 (none/normal) to 4 (severe). The total score is the average of the 8 item scores, for a total range of 0 (normal) to 4 (severe). Overall severity was assessed at 5 levels (0 [none, normal]; 1 [Very Mild]; 2 [Mild]; 3 [Moderate]; 4 [severe]).

  • Number of Participants With Drug-Induced Extrapyramidal Symptoms Scale (DIEPSS) Score at Day 22 [ Time Frame: Day 22 ] [ Designated as safety issue: Yes ]
    The DIEPSS is a scale used to evaluate the severity of drug induced extra-pyramidal symptoms occurring during antipsychotic drug treatment. Scale consists of 8 individual symptom scales with scores ranging from 0 (none/normal) to 4 (severe). The total score is the average of the 8 item scores, for a total range of 0 (normal) to 4 (severe). Overall severity was assessed at 5 levels (0 [none, normal]; 1 [Very Mild]; 2 [Mild]; 3 [Moderate]; 4 [severe]).

  • Number of Participants With Drug-Induced Extrapyramidal Symptoms Scale (DIEPSS) Score at Day 50 [ Time Frame: Day 50 ] [ Designated as safety issue: Yes ]
    The DIEPSS is a scale used to evaluate the severity of drug induced extra-pyramidal symptoms occurring during antipsychotic drug treatment. Scale consists of 8 individual symptom scales with scores ranging from 0 (none/normal) to 4 (severe). The total score is the average of the 8 item scores, for a total range of 0 (normal) to 4 (severe). Overall severity was assessed at 5 levels (0 [none, normal]; 1 [Very Mild]; 2 [Mild]; 3 [Moderate]; 4 [severe]).

  • Number of Participants With Drug-Induced Extrapyramidal Symptoms Scale (DIEPSS) Score at Day 78 [ Time Frame: Day 78 ] [ Designated as safety issue: Yes ]
    The DIEPSS is a scale used to evaluate the severity of drug induced extra-pyramidal symptoms occurring during antipsychotic drug treatment. Scale consists of 8 individual symptom scales with scores ranging from 0 (none/normal) to 4 (severe). The total score is the average of the 8 item scores, for a total range of 0 (normal) to 4 (severe). Overall severity was assessed at 5 levels (0 [none, normal]; 1 [Very Mild]; 2 [Mild]; 3 [Moderate]; 4 [severe]).

  • Number of Participants With Drug-Induced Extrapyramidal Symptoms Scale (DIEPSS) Score at Day 92 [ Time Frame: Day 92 ] [ Designated as safety issue: Yes ]
    The DIEPSS is a scale used to evaluate the severity of drug induced extra-pyramidal symptoms occurring during antipsychotic drug treatment. Scale consists of 8 individual symptom scales with scores ranging from 0 (none/normal) to 4 (severe). The total score is the average of the 8 item scores, for a total range of 0 (normal) to 4 (severe). Overall severity was assessed at 5 levels (0 [none, normal]; 1 [Very Mild]; 2 [Mild]; 3 [Moderate]; 4 [severe]).

  • Number of Participants With Drug-Induced Extrapyramidal Symptoms Scale (DIEPSS) Score at Day 120 [ Time Frame: Day 120 ] [ Designated as safety issue: Yes ]
    The DIEPSS is a scale used to evaluate the severity of drug induced extra-pyramidal symptoms occurring during antipsychotic drug treatment. Scale consists of 8 individual symptom scales with scores ranging from 0 (none/normal) to 4 (severe). The total score is the average of the 8 item scores, for a total range of 0 (normal) to 4 (severe). Overall severity was assessed at 5 levels (0 [none, normal]; 1 [Very Mild]; 2 [Mild]; 3 [Moderate]; 4 [severe]).

  • Number of Participants With Drug-Induced Extrapyramidal Symptoms Scale (DIEPSS) Score at Day 162 [ Time Frame: Day 162 ] [ Designated as safety issue: Yes ]
    The DIEPSS is a scale used to evaluate the severity of drug induced extra-pyramidal symptoms occurring during antipsychotic drug treatment. Scale consists of 8 individual symptom scales with scores ranging from 0 (none/normal) to 4 (severe). The total score is the average of the 8 item scores, for a total range of 0 (normal) to 4 (severe). Overall severity was assessed at 5 levels (0 [none, normal]; 1 [Very Mild]; 2 [Mild]; 3 [Moderate]; 4 [severe]).

  • Number of Participants With Drug-Induced Extrapyramidal Symptoms Scale (DIEPSS) Score at Day 218 [ Time Frame: Day 218 ] [ Designated as safety issue: Yes ]
    The DIEPSS is a scale used to evaluate the severity of drug induced extra-pyramidal symptoms occurring during antipsychotic drug treatment. Scale consists of 8 individual symptom scales with scores ranging from 0 (none/normal) to 4 (severe). The total score is the average of the 8 item scores, for a total range of 0 (normal) to 4 (severe). Overall severity was assessed at 5 levels (0 [none, normal]; 1 [Very Mild]; 2 [Mild]; 3 [Moderate]; 4 [severe]).


Secondary Outcome Measures:
  • Positive and Negative Syndrome Scale (PANSS) Total Score [ Time Frame: Baseline, Day 8, 22, 50, 78 and 92 ] [ Designated as safety issue: No ]
    The PANSS is a medical scale that assesses various symptoms of schizophrenia. The symptoms are rated on a 7-point scale from 1 (absent) to 7 (extreme psychopathology). The total score is the sum of all 30 PANSS items, with a range of 30 (absent) to 210 (extreme ill).

  • Number of Participants With Clinical Global Impression Severity (CGI-S) Score [ Time Frame: Baseline, Day 8, 22, 50, 78 and 92 ] [ Designated as safety issue: No ]
    The CGI-S rating scale is a 7 point (1-absent, 2-minimal, 3-mild, 4-moderate, 5-moderate severe, 6-severe, 7-extreme) global assessment that measures the clinician's impression of the severity of illness exhibited by a participant. A rating of 1 is equivalent to "normal, not at all ill" and a rating of 7 is equivalent to "among the most extremely ill participants". Higher scores indicate worsening.


Enrollment: 56
Study Start Date: January 2007
Study Completion Date: April 2008
Primary Completion Date: April 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Paliperidone palmitate 50 mg
Paliperidone palmitate 50 milligram (mg) intramuscular (into the muscle) injection on Days 1, 8, 36 and 64.
Drug: Paliperidone palmitate
Paliperidone palmitate aqueous suspension for injection 0.5, 1.0, 1.5 milliliter equivalent to 50, 100, 150 mg paliperidone respectively as intramuscular injection on Days 1, 8, 36 and 64.
Other Name: JNS010
Experimental: Paliperidone palmitate 100 mg
Paliperidone palmitate 100 mg intramuscular injection on Days 1, 8, 36 and 64.
Drug: Paliperidone palmitate
Paliperidone palmitate aqueous suspension for injection 0.5, 1.0, 1.5 milliliter equivalent to 50, 100, 150 mg paliperidone respectively as intramuscular injection on Days 1, 8, 36 and 64.
Other Name: JNS010
Experimental: Paliperidone palmitate 150 mg
Paliperidone palmitate 150 mg intramuscular injection on Days 1, 8, 36 and 64.
Drug: Paliperidone palmitate
Paliperidone palmitate aqueous suspension for injection 0.5, 1.0, 1.5 milliliter equivalent to 50, 100, 150 mg paliperidone respectively as intramuscular injection on Days 1, 8, 36 and 64.
Other Name: JNS010
Experimental: Paliperidone palmitate 150/ 50 mg
Paliperidone palmitate 150 mg intramuscular injection on Day 1 and paliperidone palmitate 50 mg intramuscular injection on Days 8, 36 and 64.
Drug: Paliperidone palmitate
Paliperidone palmitate aqueous suspension for injection 0.5, 1.0, 1.5 milliliter equivalent to 50, 100, 150 mg paliperidone respectively as intramuscular injection on Days 1, 8, 36 and 64.
Other Name: JNS010

Detailed Description:

This is a multicenter (when more than one hospital or medical school team work on a medical research study), open-label (all people know the identity of the intervention), randomized (the study drug is assigned by chance), parallel-group (Each group of participants will be treated at the same time), comparison study to assess the pharmacokinetics and safety of paliperidone palmitate (study medication) in participants with schizophrenia. The study comprises a 64-day Treatment period and a 155-day Follow-up period. The participants will be randomly assigned to one of the four study groups. The study medication will be administered on Days 1, 8, 36 and 64. Pharmacokinetics of the study medication will be assessed as primary outcome. Participants' safety will be monitored throughout the study.

  Eligibility

Ages Eligible for Study:   20 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria

  • Participants who have been diagnosed with schizophrenia in accordance with the diagnostic criteria of Diagnostic and Statistical Manual of Mental Disorders 4th edition (DSM-IV)
  • Participants may be inpatients or outpatients
  • Participants who have been taking an oral antipsychotic medication for at least 28 days before the date of informed consent
  • Participants with a Positive and Negative Syndrome Scale (PANSS) score of less than or equal to 4 (moderate) at screening
  • Participants who have taken risperidone by the start of investigational treatment and the record can be confirmed Exclusion Criteria
  • Participants who have been diagnosed with a mental disease other than schizophrenia in accordance with the diagnostic criteria of Diagnostic and Statistical Manual of Mental Disorders 4th edition (DSM-IV)
  • Participants who have been diagnosed with substance-related disorders (except nicotine and caffeine dependence)
  • Participants with complicated parkinson's disease (a progressive disorder of the central nervous system, seen usually in older persons, in which there is muscle weakness, trembling and sweating)
  • Participants with a complication of or with a history of convulsive disease such as epilepsy (seizure disorder)
  • Participants with a complication of or with a history of cerebro-vascular accident (stroke), neuroleptic malignant syndrome (high fever, rigid muscles, shaking, confusion, sweating more than usual, increased heart rate or blood pressure, or muscle pain or weakness) or physical exhaustion associated with the state of dehydration (lose of water and minerals in the body) or malnutrition
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01606254

Locations
Japan
Ichikawa, Japan
Sponsors and Collaborators
Janssen Pharmaceutical K.K.
Investigators
Study Director: Janssen Pharmaceutical K.K., Japan Clinical Trial Janssen Pharmaceutical K.K.
  More Information

No publications provided

Responsible Party: Janssen Pharmaceutical K.K.
ClinicalTrials.gov Identifier: NCT01606254     History of Changes
Other Study ID Numbers: CR013612, PALM-JPN-2
Study First Received: May 15, 2012
Results First Received: March 4, 2013
Last Updated: May 28, 2013
Health Authority: Japan: Pharmaceuticals and Medical Devices Agency

Keywords provided by Janssen Pharmaceutical K.K.:
Schizophrenia
Paliperidone Palmitate
JNS010

Additional relevant MeSH terms:
Schizophrenia
Schizophrenia and Disorders with Psychotic Features
Mental Disorders
9-hydroxy-risperidone
Antipsychotic Agents
Tranquilizing Agents
Central Nervous System Depressants
Physiological Effects of Drugs
Pharmacologic Actions
Central Nervous System Agents
Therapeutic Uses
Psychotropic Drugs

ClinicalTrials.gov processed this record on August 01, 2014